The long-term objectives of this research program is a detailed understanding of age-related changes in the neuronal organization of the hippocampal formation, and the role that these neural alterations play in the decline of memory with age. There are two principal reasons for studying the changes in neurological and cognitive function which occur with normal aging. First, such data are a necessary prerequisite to the development of therapeutic measures to deal with the specific problems of the elderly. Second, the aging process involves definable alterations in neural structure and function which are associated with characteristic changes in behavior. The correlation of these alterations may be used to clarify neural mechanisms of behavior at all age levels. The discovery of how and why learning and memory are altered over the lifespan requires the integration of behavioral and neurobiological methods, and a principal goal of this research is to bring these different levels of analysis to bear on the specific problem of loss of spatial memory capacity in old rats. The methods involve behavioral analysis of spatial navigation and contextual memory, intra-and extracellular recording in the in vitro hippocampal slice preparation, and extra cellular recording of synaptic potentials in the behaving rat. Three specific questions with respect to memory alterations with age are addressed in this proposal: 1) the effect of age on hippocampal involvement in the memory consolidation process, 2) identification of the mechanisms that cause long-term synaptic enhancement to be defective in old rats, and 3) the role of estrogen in possible cyclical changes in hippocampal synaptic transmission in female rats. The latter studies are intended to provide preliminary data on possible sex differences in the manner in which learning and memory systems decline with age. The overall theme of the proposed experiments derives from work in the past grant periods in which mechanisms underlying the induction and maintenance of synaptic plasticity have been examined in relation to behavior. The implication of more rapid decay of synaptic enhancement and spatial memory in old rats will be examined in the memory consolidation experiments. The latter two experiments will directly examine whether NMDA-dependent induction processes, or synapse sparsity is responsible for the age or sex differences observed in synaptic plasticity. The experiments proposed here are intended to provide a more detailed understanding both of how memory is affected by the aging process in males and females, and the most likely causes of these changes at the level of cellular interactions. Answers to these questions should provide insights into how age-related changes at the cellular level translate into alterations of cognitive decline during the normal aging process.